The proposed research program involves an extensive study of ion transport by rabbit colon in vitro which will include: (a) studies of the bidirectional fluxes of Na, Cl and K under short-circuit conditions; (b) determination of net transepithelial transport of bicarbonate; (c) determination of unidirectional influxes of Na, Cl and K across the mucosal membranes; (d) determination of intracellular ionic concentrations and thermodynamic activities; (e) studies of the properties of the passive conductance pathways across the tissue; (f) determination of intracellular electrical potentials and the transepithelial electrical potential profile; and (g) studies of the metabolic properties of the tissue. The overall aim is to (1) characterize the mechanisms responsible for ion transport by rabbit colon under control conditions; (2) examine the effects of humoral and pharmacologic agents that appear to affect colonic function; and (3) define the mechanisms by which bile salts and hydroxy-fatty acids impair colonic absorptive processes and appear to elicit active secretion by the large intestine. The results of these studies should not only provide a basis for the understanding of normal function but should provide insights into the mechanisms of action of several humoral and pharmacologic agents as well as the processes responsible for impairment of colonic function during steatorrhea and following ileal resection.